caa a22 4500 60550721X CHVBK 20210128100631.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00775-015-1298-7 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1298-7 Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model [Elektronische Daten] [I. León, J. Cadavid-Vargas, I. Tiscornia, V. Porro, S. Castelli, P. Katkar, A. Desideri, M. Bollati-Fogolin, S. Etcheverry] Vanadiumcompounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na2[VO(silibinin)2]·6H2O (VOsil) and chrysin [VO(chrysin)2EtOH]2 (VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments. Graphical Abstract: SBIC, 2015 Metal based drug nationallicence HT-29 human colon adenocarcinoma cells nationallicence Mechanisms of action nationallicence Flavonoids nationallicence Vanadium nationallicence León I. Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina aut Cadavid-Vargas J. Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina aut Tiscornia I. Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay aut Porro V. Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay aut Castelli S. Department of Biology, University of Rome "Tor Vergata”, Rome, Italy aut Katkar P. Department of Biology, University of Rome "Tor Vergata”, Rome, Italy aut Desideri A. Department of Biology, University of Rome "Tor Vergata”, Rome, Italy aut Bollati-Fogolin M. Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay aut Etcheverry S. Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/7(2015-10-01), 1175-1191 0949-8257 20:7<1175 2015 20 775 https://doi.org/10.1007/s00775-015-1298-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1298-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- León I. Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina aut NATIONALLICENCE 700 1- Cadavid-Vargas J. Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina aut NATIONALLICENCE 700 1- Tiscornia I. Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay aut NATIONALLICENCE 700 1- Porro V. Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay aut NATIONALLICENCE 700 1- Castelli S. Department of Biology, University of Rome "Tor Vergata”, Rome, Italy aut NATIONALLICENCE 700 1- Katkar P. Department of Biology, University of Rome "Tor Vergata”, Rome, Italy aut NATIONALLICENCE 700 1- Desideri A. Department of Biology, University of Rome "Tor Vergata”, Rome, Italy aut NATIONALLICENCE 700 1- Bollati-Fogolin M. Unidad de Biología Celular, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay aut NATIONALLICENCE 700 1- Etcheverry S. Cátedra de Bioquímica Patológica, Facultad Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/7(2015-10-01), 1175-1191 0949-8257 20:7<1175 2015 20 775